tbuckley/cabot-search huggingface dataset:
Abstract 15180: Cerebral Blood Flow Measured by Mri is a Key Translational Hallmark of Brain Injury in Experimental Models of Hypertension-Induced Cognitive Impairment
Authors: Lorenzo Carnevale, Raimondo Carnevale, Marialuisa Perrotta, Francesco Mastroiacovo, Daniela Carnevale, Giuseppe Lembo
Journal: Circulation (2022)

While several works pointed out the epidemiological associations between hypertension and dementia, the underlying mechanisms are still relatively unknown. In this work we focused on the application of translational tools like MRI to investigate the brain injury induced by hypertension and characterized by cognitive impairment and neuroinflammation. Cerebral hypertension was induced in mice by transverse aortic constriction (TAC) or sham procedure, as previously demonstrated by our group. We characterized cerebral blood flow (CBF) by 7T MRI, measuring the cerebral tissue blood prefusion. Morris Water Maze (MWM) was used to evaluate cognitive function in hypertensive and normotensive mice. Cortical microvasculature was analyzed in histological brain sections. A group of mice was treated with an antibody neutralizing IFNy, a key proinflammatory cytokine induced by hypertension. TAC mice showed a marked cerebral hypoperfusion, with CBF reduction in cortex (Sham: 96.58 vs TAC: 74.25 mL/100g/min p=0.024) and hypothalamus (Sham: 140 vs TAC: 121.4 mL/100g/min p=0.027). Tissue analysis revealed a reduction in capillary density defined as portion of field of view (FOV) occupied by capillaries (Sham: 11.3% vs TAC: 7.7%, p=0.004) and loss of their integrity in the cortex of hypertensive mice, defined as pericyte coverage percentage in the FOV (Sham: 79% vs TAC: 36%, p=0.01). Finally, the impairment in cognitive function measured by the MWM correlated with the CBF measures (r 2 :0.407, p=0.01). In the end, we subjected TAC mice to anti-IFNy treatment and analyzed the effects on brain vasculature assessed in vivo by MRI and ex vivo by histology. We observed that, while leaving unchanged the hemodynamic challenge on the brain, the treatment induced a global rescue in CBF (TAC: 99.85 vs TAC anti-IFNy: 116 mL/100g/min p=0. 008) and a strong correlation between MRI-measured CBF and microvascular density (r 2 :0.471, p=0.002). In conclusion, CBF evaluated by MRI is a key translational hallmark of hypertensive brain injury, and its evaluation in the clinical setting can provide insights on cerebral microvasculature health.
Abstract 14451: Mechanistic Classification and Outcomes of Isolated Aortic Regurgitation in a Contemporary Cohort of Patients
Authors: Rudy R Unni, Jiaming (Calvin) Liang, Ibrahim Jelaidan, David Harnett, Munir Boodhwani, David Glineur, Ian G Burwash, Kwan L Chan, Thais Coutinho, Graeme Prosperi-Porta, Angel Yi Nam Fu, Nadav Willner, David Messika-Zeitoun, Luc M Beauchesne
Journal: Circulation (2022)

Introduction: Aortic valve regurgitation (AR) is due to leaflet disease and/or dilatation of the functional aortic annulus complex. Understanding the mechanism(s) of AR informs surgical planning of valve and aorta repair. In this study we aimed to examine the etiologies, mechanisms, and outcomes of isolated pure native severe AR in a contemporary consecutive cohort of patients. Methods: From our institutional echocardiography database, we identified all patients with native moderate-to-severe (3+) or severe (4+) AR between 2014-2019. Patients with infective endocarditis, aortic dissection, or other concomitant valve disease were excluded. AR was classified using the El-Khoury classification: Type I-normal leaflet motion (Ia = ascending aorta and sinotubular junction dilatation, Ib = aortic root dilation, Ic = aortic annular dilation), Type II-leaflet prolapse, and Type III-leaflet restriction. Valve anatomy and clinical outcomes were also extracted. Results: A total of 560 patients with at least moderate-to-severe (3+) AR were identified, 270 were excluded (92 patients for endocarditis, 152 patients for concomitant valvulopathy, 23 patients for acute aortic dissection, and 11 patients for other reasons), and 282 patients (77.3% male) were included. The most common mechanism was Type II (leaflet prolapse), idenfied in 98 (35%) patients. Multiple mechanisms of AR were identified in 164 (58%) patients. The most common combination was Type Ib (aortic root dilation) and Type II (leaflet prolapse) seen in 45 (27%) patients. Ninety-nine (35%) patients had a bicuspid aortic valve (BAV). Follow-up was available for 275 patients (98%) with a median duration of 4.7±2.4 years. Of the 158 (57%) patients who underwent surgical intervention, valve repair was performed in 77 patients (49%) and valve replacement in 80 (51%) patients. Valve intervention was more common in women (70%) than in men (54%). Conclusion: In a large contemporary cohort of patients with at least moderate to severe (3+) isolated pure native AR, Type II (leaflet prolapse) was the most common mechanism, however multiple mechanisms are present in most AR patients. Aortic valve repair now accounts for almost half of the surgical interventions for isolated AR in our center.
Abstract 14986: Reduced Arrhythmia Recurrence at One-Year When Using Active Esophageal Cooling
Authors: Christopher Joseph, Charles Athill, Annie Ruppert, Danya Willms, Gregory Francisco
Journal: Circulation (2022)

Introduction: The use of active esophageal cooling instead of traditional luminal esophageal temperature (LET) monitoring during left atrial ablation for the treatment of atrial fibrillation (AF) allows contiguous lesion placement with fewer partially-formed lesions and less catheter repositioning than required with LET monitoring. As a consequence, fewer electrical reconnections, and a lower rate of atrial arrhythmia recurrence, may result. We aimed to determine the association between esophageal protective strategy and recurrence of arrhythmia at one-year. Methods: We performed an IRB-approved review of an existing hospital registry to measure the association between recurrence of arrhythmia at one year follow-up and the use of active esophageal cooling as opposed to LET monitoring. Data were collected from ablations performed between 2017 and 2020. For each patient we recorded the type of esophageal temperature management, rhythm status at one-year follow-up, ejection fraction, and CHA 2 DS 2 -VASc score. Results: Data from a total of 247 ablations were collected. There were 95 ablations that occurred in the actively cooled group and 152 in the LET monitored group. Among those in the actively cooled group, the average CHA 2 DS 2 -VASc score was 1.8, and the average ejection fraction was 61%. In the LET monitored group, the average CHA 2 DS 2 -VASc score was 1.2 and the average ejection fraction was 61%. In the LET monitored group, there were 36 patients who had atrial arrhythmias at one-year follow-up, representing a 24% recurrence rate. In the actively cooled group, 11 patients had recurrence of arrhythmia at one-year, representing a 12% recurrence rate (P=0.02). Conclusions: Patients treated with active esophageal cooling during left atrial ablation had a significantly lower atrial arrhythmia recurrence rate at one-year follow-up when compared to patients provided with traditional LET monitoring during left atrial ablation procedures.
Abstract 15238: Impact of Statins on All-Cause Mortality in Subjects With Severe Coronary Artery Calcium Score: Results Form the Confirm (Coronary Ct Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) Registry
Authors: Dhiran Verghese, April Kinninger, Venkat S Manubolu, Jairo Aldana-Bitar, Luay Hussein Alalawi, James K Min, James Earls, Stephan Achenbach, Ashley Dunham, Tami Crabtree, Heidi Gransar, Mouaz Al-Mallah, Jeroen J Bax, Daniel S Berman, Filippo Cademartiri, Tracy Callister, Hyuk-Jae Chang, Benjamin J Chow, Ricardo C Cury, Gudrun M Feuchtner, Martin Hadamitzky, Joerg Hausleiter, Philipp A Kaufmann, Jonathon Leipsic, Fay Y Lin, Yong-Jin Kim, Hugo Marques, Gianluca Pontone, Ronen Rubinshtein, Todd Villines, Leslee J Shaw, Matthew Budoff
Journal: Circulation (2022)

Introduction: Coronary artery calcium (CAC) score improves prognostic accuracy of atherosclerotic cardiovascular disease outcomes. However, the relative impact of statins on outcomes stratified by CAC score is limited. Methods: The open-label, 12-center, 6-country prospective longitudinal CONFIRM registry was queried. Individuals with severe CAC (≥300), with long term follow up were selected. Subjects with prior ASCVD events were excluded. The primary study end point was all-cause mortality (ACM) which was compared in individuals on stain versus those not on statin. Kaplan-Meier cumulative incidence curves were performed and compared with log rank test. Multivariate Cox proportional hazard regression analysis was used to calculate hazard ratio (HR) with 95% confidence interval (CI). Results: Of 21,863 participants from the CONFRIM registry, 5,928 had no prior ASCVD events and had information on CAC and statin use. Of these, 972 had a CAC score of ≥300. The mean age of statin users and non-users with CAC≥300 was similar at 67.7± 9.0 vs. 66.9±10.5; p=0.166, and both groups were predominantly male (70% vs 69%, p=0.736). Statin users were more likely to have high cholesterol (93% vs 43%), hypertension (74% vs. 67%), diabetes mellitus (27% vs 20%), family history of cardiovascular disease (41% vs. 34%) and less likely to be a current smoker (22% vs 34%); all p&lt;0.05. There were 42 (9%) deaths over a mean follow-up of 4.2 years among statin users and 86 (18%) deaths over 3.9 years in non-users. In multivariable proportional hazard Cox modeling with a reference group of non-statin users, statin participants with CAC of ≥300 had significantly reduced risk for ACM, HR 0.52- (95% CI, 0.33-0.82, p=0.005). Conclusions: In this large prospective registry, in the primary prevention cohort of patients without prior ASCVD events, severe CAC ≥ 300 identified patients most likely to benefit from statin use. Statins lowered ACM in patients with CAC≥ 300 by 48%.
Abstract 15176: Development of Femoral Artery Denervation Models for Vascular Remodeling
Authors: Taylor K Brown, Liqun Xiong, Sara Alharbi, Karen Ho, Bin Jiang
Journal: Circulation (2022)

Introduction: Restenosis is a common cause of vascular device failure. An important contributor is the transdifferentiation of vascular smooth muscle cells (VSMCs) from a contractile to synthetic phenotype. Healthy arteries are innervated by sympathetic nerves to regulate VSMC contractility and phenotype, yet this interaction has been overlooked in pathological vascular remodeling such as restenosis. Hypothesis: Sympathetic denervation of the femoral artery will lead to transdifferentiation of arterial VSMC and pathological remodeling of the arterial structure. Methods: The femoral arteries of male BALB/c mice were surgically exposed and treated with specific dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) or vehicle for 5 minutes. In the model of long-term denervation, the mice were subcutaneously injected with 6-OHDA or vehicle weekly for 4 weeks. Femoral arteries and peri-adventitial tissue were harvested for histology. Innervation density was calculated as the number of sympathetic nerve fibers (tyrosine hydroxylase-positive) normalized to the medial layer area (α-smooth muscle actin-positive). Extracellular matrix (ECM) composition was visualized with Masson’s trichrome and Verhoeff's elastic staining. Results: One week after surgery, 6-OHDA-treated arteries had a notable reduction in sympathetic nerve density compared to controls (2.9 vs. 11.7 fibers/10,000 μm 2 [P=.22, n=2]). This difference decreased at 2 weeks (6.8 vs. 8.0 fibers/10,000 μm 2 [P=0.50, n=3]) and at 4 weeks (4.4 vs. 5.0 fibers/10,000 μm 2 [P=0.83, n=3]), suggesting nerve recovery. No difference was observed in ECM composition. Tissues harvested at 1 and 4 weeks in the 6-OHDA injection model demonstrate qualitative denervation of the treated limb compared to control. Conclusions: Sympathetic denervation of murine femoral arteries can be achieved by direct surgical application or subcutaneous injection of 6-OHDA. Future work will characterize vascular remodeling after long-term denervation and combine denervation with vascular injury. If a causal relationship can be identified between sympathetic denervation and VSMC pathology, engineering reinnervation could be a viable approach for future graft design.
Abstract 14790: Impact of Pre-Frailty and Frailty in Women Undergoing TAVR: Insights From the WIN-TAVI Registry
Authors: Marija Petrovic, Alessandro Spirito, Samantha Sartori, Clayton Snyder, Birgit Vogel, Johny Nicolas, Rebecca M Cohen, Davide Cao, Didier Tchetche, Anna S Petronio, Julinda Mehilli, Thierry Lefevre, Patrizia Presbitero, Piera Capranzano, ALESSANDRO IADANZA, Gennaro Sardella, Nicolas M Van Mieghem, emanuele meliga, Nicolas DUMONTEIL, Chiara Fraccaro, Daniela Trabattoni, Ghada Mikhail, Maria-Cruz Ferrer-Gracia, Christoph Naber, Peter C Kievit, Samin K Sharma, Marie C Morice, George Dangas, Alaide Chieffo, Roxana Mehran
Journal: Circulation (2022)

Background: Frailty has been shown to significantly affect outcomes after transcatheter aortic valve replacement (TAVR). The impact of pre-frailty on TAVR outcomes in women is still unclear. Aim: To assess the impact of pre-frailty and frailty on outcomes in women enrolled in the Women's InterNational transcatheter aortic valve implantation (WIN-TAVI) registry. Materials and methods: WIN-TAVI was a multinational, prospective, observational registry, which enrolled women at intermediate or high preoperative risk undergoing TAVR. Patients included in this registry were divided into three groups, based on the number of fulfilled Fried frailty criteria: non-frail (no criteria, reference group), pre-frail (1-2 criteria) and frail (≥3 criteria). The primary outcome was the Valve Academic Research Consortium (VARC)-2 efficacy endpoint at 1-year after TAVR. The key secondary outcome was VARC-2 safety endpoint. Results: Out of 1,019 patients, 264 (25.9%) were pre-frail and 33 (3.2%) frail. The risk of VARC-2 efficacy endpoint at 1-year was increased in pre-frail (19.7%, HR 1.36, 95% CI 0.98-1.89) and frail (24.2%, HR 1.74, 95% CI 0.85-3.57) as compared to non-frail patients (14.9%, reference group), although it didn’t reach statistical significance. The risk of VARC-2 safety endpoint was significantly higher in pre-frail (25.8%, HR 1.43, 95% CI 1.07-1.91) and frail (42.4%, HR 2.77, 95% CI 1.60-4.80) than in non-frail subjects (19%, reference group); this difference was driven by an excess of major vascular complications and life-threatening or major bleeding in the pre-frail and frail group. In addition, in pre-frail patients hospitalizations for heart failure or valve-related symptoms at 1-year were higher than in non-frail patients. Conclusion: In women at intermediate or high preoperative risk undergoing TAVR, pre-frailty and frailty increased the risk of safety endpoints such as vascular complications and major bleeding.
Abstract 15016: Inferior ST Segment Depression Identifies Proximal Left Anterior Descending Culprit Lesions in Anterior ST Elevation Myocardial Infarction
Authors: Brian Anyanwu, Sim Berlene Mariano, Miles Shen, Lefan He, Bobby D Ghosh, Ashok Chaudhary, John Kassotis, James Coromilas
Journal: Circulation (2022)

Introduction: Anterior wall ST elevation myocardial infarction (STEMI) is caused by occlusion of the left anterior descending (LAD) coronary artery. Proximal LAD occlusions are associated with larger infarcts and more complications. However, there is limited data demonstrating a relationship between ECG changes and the location of the LAD culprit lesion. Objective: To determine if patterns of ST elevations (STE)/depressions (STD) on the 12 lead ECG can predict if the culprit lesion in an anterior STEMI is in the proximal LAD. Methods: We performed a retrospective chart review of ECGs obtained from a database of patients diagnosed with myocardial infarction at Robert Wood Johnson University Hospital from January 2009 to December 2016. Lesions, defined as proximal or non-proximal with respect to the first diagonal of the LAD, were assigned according to the Bypass Angioplasty Revascularization Investigation (BARI) Protocol. Each lesion was assigned to one of the 4 ECG patterns described in Table 1. An analysis of variance was used to determine if the difference in ECG characteristics between groups was significant. Results: Of 447 ECGs denoted as anterior wall STEMIs, 227 met inclusion criteria. In total, 104 lesions were defined as proximal and 123 were non-proximal. There was a difference in the ECG pattern of proximal versus non-proximal culprits category (p = 0.006). Proximal culprit lesions were more likely to have STE in the precordial leads combined with STD in the inferior leads, whereas non-culprit lesions were more likely to have STE in the precordial leads without any STE or STD in the limb leads. Conclusions: In anterior STEMIs, proximal culprit lesions were more likely to exhibit ST elevations in precordial leads and ST depressions in inferior leads, compared to non-proximal culprit lesions, which were more likely to have ST elevations in only the precordial leads. Concomitant STE in lateral leads without inferior STD did not distinguish between the 2 groups.
Abstract 14799: Sex Differences in Health Status Decline of Patients With Aortic Valve Stenosis: Results From the Progressa Study
Authors: Lionel Tastet, Mylene Shen, Romain Capoulade, Kathia Abdoun, Marie-Ange Fleury, Marie Arsenault, Elisabeth Bédard, Philippe Pibarot, Marie-Annick A Clavel
Journal: Circulation (2022)

Introduction: The assessment of symptoms status is pivotal to optimize the timing of aortic valve intervention in aortic stenosis (AS). However, little is known about the effect of sex on health status decline (i.e. functional status and quality of life) in AS patients. We evaluated the change in health status according to sex in patients with mild to moderate AS. Methods: Two hundred eighty-five patients with AS (peak aortic jet velocity [V peak ]≥2.0 m/s) prospectively recruited in the PROGRESSA study (NCT01679431) were included in this analysis. Health status was evaluated using the New York Heart Association (NYHA) classification and the Duke Activity Score Index (DASI). Results: At baseline, men were older (67±12 vs 61±17 yr; p=0.001), had more comorbidities including hypertension, coronary artery disease, and atrial fibrillation (all, p≤0.01), and more severe AS compared to women (2.8±0.5 vs 2.6±0.4 m/s; p=0.01). However, women had more symptoms (class I, II, III: 44%, 53%, 3% versus 63%, 36%, 1%; p=0.02) and significantly lower DASI (38±14 vs 43±13; p=0.006). During a mean follow-up of 3.9±2.4 years, despite faster AS progression rate in men (V peak increase: 0.16±0.2 vs 0.12±0.2 m/s/year; p=0.02), the worsening of symptoms (NYHA ≥I class; n=70) and decline in DASI score were comparable according to sex (Figure). However, for the same hemodynamic AS progression rate, women had significantly faster decline in DASI score (Figure). In linear mixed analysis adjusted for several clinical and echocardiographic risk factors, female sex remained significantly associated with the worsening of NYHA class (odds ratio: 3.9; 95% CI: 2.1 to 7.2; p&lt;0.0001) and the decline in DASI score (coeff.: -9; 95% CI: -11 to -6; p&lt;0.0001). Conclusion: Despite a better clinical profile and less severe AS, women generally had worse symptomatic status compared to men, and this difference was accentuated throughout follow-up. These findings raise the question of symptoms minimisation in women.
Abstract 14782: Expression of Ngf Shrna in the Left Atrial Appendage Alone is Sufficient to Attenuate Global Left Atrial Parasympathetic and Sympathetic Nerve Sprouting and Resulting Development of Persistent Atrial Fibrillation in a Canine Model
Authors: Anna Pfenniger, Shin Yoo, David Johnson, Wenwei Zhang, Azaria Panni, Amy Burrell, Suman Mandava, Markus Rottmann, Rod S Passman, Bradley P Knight, Rishi Arora
Journal: Circulation (2022)

Introduction: The autonomic nervous system plays a major role in development of atrial fibrillation (AF), with evidence of marked autonomic remodeling in a canine rapid atrial pacing (RAP) model of AF. Nerve growth factor (NGF), a neurotrophin essential for peripheral neuron growth, was upregulated in fibrillating atria, particularly in the left atrial appendage (LAA). Hypothesis: Inhibiting NGF signaling in the entire atria or the LAA alone can prevent the development of AF. Methods: NGF shRNA was injected in both atria or in the LAA of dogs followed by electroporation to facilitate gene delivery. Animals were subjected to RAP for up to 12 weeks. Duration of AF was recorded. At terminal EP study, residual AF electrograms were recorded in the posterior left atrium, left atrial free wall and LAA for analysis of AF characteristics. Tissue of each region was used for IHC with markers for parasympathetic (acetylcholinesterase) or sympathetic nerves (dopamine beta-hydroxylase). Results: Controls (n=10) developed persistent AF (&gt;8 hours) after a median of 14 days. In contrast, pan-atrial NGF shRNA animals (n=4) never developed this burden of AF. Residual AF was less fractionated (longer fractionation interval), more organized (higher organization index and lower Shannon's entropy) and more homogeneous (coefficient of variation of dominant frequency). RAP-induced nerve bundle hypertrophy and atrial myocardium hyperinnervation was significantly attenuated in pan-atrial NGF shRNA dogs. Importantly, these findings were reproduced when NGF shRNA injection was limited to the LAA alone (n=4), with prevention of development of persistent AF, and global attenuation of left atrial hyperinnervation. Conclusion: Targeted inhibition of atrial autonomic remodeling by NGF shRNA prevents development of persistent AF. NGF Inhibition in the LAA alone is sufficient to attenuate global atrial autonomic remodeling. This approach may lead to a novel, mechanism-guided therapy for AF.
Abstract 152: Effect Of Calcium On Patient Outcomes In Pulseless Electrical Activity With Wide QRS-Complexes
Authors: Mikael F Vallentin, Asger Granfeldt, Amalie Povlsen, Lars W Andersen
Journal: Circulation (2022)

Introduction: The Calcium for Out-of-hospital Cardiac Arrest (COCA)-trial recently found no benefit of administering calcium during out-of-hospital cardiac arrest in an unselected adult population. Still, calcium is recommended for cardiac arrest caused by hyperkalemia. Higher potassium levels have been found in cardiac arrest patients with wide QRS-complexes which may act as an indicator of hyperkalemia. Objectives: 1) To describe characteristics of patients with baseline PEA in out-of-hospital cardiac arrest, and 2) to determine the effect of calcium on return of spontaneous circulation (ROSC) in patients displaying PEA with wide and normal QRS-complexes. Methods: COCA was a randomized, double-blind, placebo-controlled trial of calcium administered immediately after the first and second epinephrine dose of adults in out-of-hospital cardiac arrest. Of the 391 included patients, this abstract included those with PEA at the last rhythm analysis prior to first trial drug administration. PEA was defined as any rhythm that was not ventricular fibrillation, ventricular tachycardia, or asystole. Wide QRS-complexes were defined as &gt; 110 ms. Results: 104 patients had baseline PEA and available electrocardiograms. Demographics and electrocardiographic characteristics are presented in Table 1. The median heart rate was 42, half presented with an escape rhythm, and 70% had wide QRS-complexes. Half exhibited ST-elevation. The overall ROSC-rate was 31%. The relative risk of ROSC for patients receiving calcium as compared to placebo was 0.75 (95% confidence interval (CI) 0.33-1.72) in the normal QRS-group and 0.82 (95% CI 0.47-1.41) in the wide QRS-group. Conclusion: In adults with out-of-hospital cardiac arrest, baseline PEA rhythms often included bradycardia, escape rhythms, wide QRS-complexes, and/or ST-elevation. The effects of calcium administration on ROSC were similar in a subgroup analysis of normal vs. wide QRS-complexes.